Reactive stroma and trastuzumab resistance in HER2-positive early breast cancer

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http://hdl.handle.net/10138/327113

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Sonnenblick , A , Salmon-Divon , M , Salgado , R , Dvash , E , Pondé , N , Zahavi , T , Salmon , A , Loibl , S , Denkert , C , Joensuu , H , Ameye , L , Van den Eynden , G , Kellokumpu-Lehtinen , P-L , Azaria , A , Loi , S , Michiels , S , Richard , F & Sotiriou , C 2020 , ' Reactive stroma and trastuzumab resistance in HER2-positive early breast cancer ' , International Journal of Cancer , vol. 147 , no. 1 , pp. 266-276 . https://doi.org/10.1002/ijc.32859

Title: Reactive stroma and trastuzumab resistance in HER2-positive early breast cancer
Author: Sonnenblick, Amir; Salmon-Divon, Mali; Salgado, Roberto; Dvash, Efrat; Pondé, Noam; Zahavi, Tamar; Salmon, Asher; Loibl, Sibylle; Denkert, Carsten; Joensuu, Heikki; Ameye, Lieveke; Van den Eynden, Gert; Kellokumpu-Lehtinen, Pirkko-Liisa; Azaria, Amos; Loi, Sherene; Michiels, Stefan; Richard, Francois; Sotiriou, Christos
Contributor: University of Helsinki, Doctoral Programme in Biomedicine
Date: 2020-07-01
Language: eng
Number of pages: 11
Belongs to series: International Journal of Cancer
ISSN: 0020-7136
URI: http://hdl.handle.net/10138/327113
Abstract: We investigated the value of reactive stroma as a predictor for trastuzumab resistance in patients with early HER2-positive breast cancer receiving adjuvant therapy. The pathological reactive stroma and the mRNA gene signatures that reflect reactive stroma in 209 HER2-positive breast cancer samples from the FinHer adjuvant trial were evaluated. Levels of stromal gene signatures were determined as a continuous parameter, and pathological reactive stromal findings were defined as stromal predominant breast cancer (SPBC; >= 50% stromal) and correlated with distant disease-free survival. Gene signatures associated with reactive stroma in HER2-positive early breast cancer (N = 209) were significantly associated with trastuzumab resistance in estrogen receptor (ER)-negative tumors (hazard ratio [HR] = 1.27 p interaction = 0.014 [DCN], HR = 1.58, p interaction = 0.027 [PLAU], HR = 1.71, p interaction = 0.019 [HER2STROMA, novel HER2 stromal signature]), but not in ER-positive tumors (HR = 0.73 p interaction = 0.47 [DCN], HR = 0.71, p interaction = 0.73 [PLAU], HR = 0.84; p interaction = 0.36 [HER2STROMA]). Pathological evaluation of HER2-positive/ER-negative tumors suggested an association between SPBC and trastuzumab resistance. Reactive stroma did not correlate with tumor-infiltrating lymphocytes (TILs), and the expected benefit from trastuzumab in patients with high levels of TILs was pronounced only in tumors with low stromal reactivity (SPBC
Subject: HER2
breast cancer
reactive stroma
CAF
TILs
TUMOR MICROENVIRONMENT
GENE-EXPRESSION
TGF-BETA
ADJUVANT THERAPY
DOUBLE-BLIND
CELLS
FIBROBLASTS
HETEROGENEITY
MULTICENTER
CARCINOMAS
3122 Cancers
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